Molecular Probes for Detecting Lipids

Abstract

A method of detecting aberrant lipid accumulation in a subject includes administering to the subject a molecular probe that includes a fluorescent trans stilbene derivative or stilbenzene derivative and detecting the amount or distribution of the molecular probe in a tissue of interest of the subject.

1 : A method of detecting aberrant lipid accumulation in a tissue of interest of a subject, the method comprising:
 administering to the tissue of interest of the subject a molecular probe comprising a compound selected from the group consisting of:   
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 14  and R 15  are each independently a hydrophilic or lipophilic group; wherein each X 1 , X 2 , and X 3  is a double or triple bond; each R 4 -R 13  and R 17 -R 26  is independently selected from the group consisting of H, F, Cl, Br, I, a lower alkyl group, an alkylene group, an alkenyl group, an alkynyl group, an alkoxy group, an aryl group, an aryloxy group, an alkaryl group, an aralkyl group, O, (CH 2 ) n OR′ (wherein n=1, 2, or 3), CF 3 , CH 2 —CH 2 X, O—CH 2 —CH 2 X, CH 2 —CH 2 —CH 2 X, O—CH 2 —CH 2 X (wherein X═H, F, Cl, Br, or I), CN, C═O, (C═O)—R′, N(R′) 2 , NO 2 , (C═O)N(R′) 2 , O(CO)R′, OR′, SR′, COOR′, R ph , CR′═CR′—R ph , CR 2 ′—CR 2 ′—R ph  (wherein R ph  represents an unsubstituted or substituted phenyl group, wherein R′ is H or a substituted or unsubstituted lower alkyl group); wherein R 10  and R 11  and/or R 12  and R 13  may be linked to form a cyclic ring, wherein the cyclic ring is aromatic, alicyclic, heteroaromatic, or heteroalicyclic; or a pharmaceutically acceptable salt thereof; and 
         detecting the amount or distribution of the molecular probe in the tissue of interest of the subject, wherein the amount or distribution of the detected molecular probe in the tissue of interest is indicative of the amount or distribution of aberrant lipid accumulation in the tissue of interest. 
       
     
     
         2 : The method of  claim 1 , the molecular probe of  claim 1  further comprising a radiolabel. 
     
     
         3 : The method of  claim 2 , the radiolabel including at least one of a  3 H,  125 I,  11 C, or  18 F. 
     
     
         4 : The method of  claim 1 , the molecular probe further comprising a chelating group or a near infrared imaging group. 
     
     
         5 : The method of  claim 1 , wherein X 1  is a double bond. 
     
     
         6 : The method of  claim 1 , wherein R 1 , R 2 , R 14 , and R 15  are amines or alkyl derivatives thereof. 
     
     
         7 : The method of  claim 1 , wherein the aberrant lipids that are accumulated comprise sphingolipids. 
     
     
         8 : The method of  claim 1 , wherein the subject has or is at risk of a lipid storage disorder. 
     
     
         9 : The method of  claim 1 , wherein the lipid storage disorder comprises Fabry disease. 
     
     
         10 : The method of  claim 1 , wherein the molecular probe is administered to the subject by parenteral administration. 
     
     
         11 : The method of  claim 1 , further comprising administering an agent to the subject prior to administering the molecular probe to the subject and comparing the detected amount or distribution of the molecular probe in the tissue of interest to a control amount or distribution, wherein a decrease in the detected amount or distribution of the molecular probe in the tissue of interest is indicative of the agent reducing the aberrant lipid accumulation in the tissue of interest. 
     
     
         12 : The method of  claim 11 , the agent administered to the subject being screened for efficacy in treating aberrant lipid accumulation associated with a lipid storage disease. 
     
     
         13 : The method of  claim 12 , the lipid storage disease being Fabry disease. 
     
     
         14 : A method of detecting sphingolipids in a tissue of interest of a subject, the method comprising:
 administering to the subject a molecular probe comprising a compound selected from the group consisting of   
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 14  and R 15  are each independently a hydrophilic or lipophilic group; wherein each X 1 , X 2 , and X 3  is a double or triple bond; each R 4 -R 13  and R 17 -R 26  is independently selected from the group consisting of H, F, Cl, Br, I, a lower alkyl group, an alkylene group, an alkenyl group, an alkynyl group, an alkoxy group, an aryl group, an aryloxy group, an alkaryl group, an aralkyl group, O, (CH 2 ) n OR′ (wherein n=1, 2, or 3), CF 3 , CH 2 —CH 2 X, O—CH 2 —CH 2 X, CH 2 —CH 2 —CH 2 X, O—CH 2 —CH 2 X (wherein X═H, F, Cl, Br, or I), CN, C═O, (C═O)—R′, N(R′) 2 , NO 2 , (C═O)N(R′) 2 , O(CO)R′, OR′, SR′, COOR′, R ph , CR′═CR′—R ph , CR 2 ′—CR 2 ′—R ph  (wherein R ph  represents an unsubstituted or substituted phenyl group, wherein R′ is H or a substituted or unsubstituted lower alkyl group); wherein R 10  and R 11  and/or R 12  and R 13  may be linked to form a cyclic ring, wherein the cyclic ring is aromatic, alicyclic, heteroaromatic, or heteroalicyclic; or a pharmaceutically acceptable salt thereof; and 
         detecting the amount or distribution of the molecular probe in the tissue of interest, wherein the amount or distribution of the detected molecular probe in the tissue of interest is indicative of the amount or distribution of sphingolipids in the tissue of interest. 
       
     
     
         15 : The method of  claim 14 , the molecular probe further comprising a radiolabel. 
     
     
         16 : The method of  claim 15 , the radiolabel including at least one of a  3 H,  125 I,  11 C, or  18 F. 
     
     
         17 : The method of  claim 14 , the molecular probe further comprising a chelating group or a near infrared imaging group. 
     
     
         18 : The method of  claim 14 , wherein X 1  is a double bond. 
     
     
         19 : The method of  claim 14 , wherein R 1 , R 2 , R 14 , and R 15  are amines or alkyl derivatives thereof. 
     
     
         20 : The method of  claim 14 , wherein the subject has or is at risk of a lipid storage disorder. 
     
     
         21 : The method of  claim 20 , wherein the lipid storage disorder is Fabry disease. 
     
     
         22 : The method of  claim 14 , wherein the molecular probe is administered to the subject by parenteral administration. 
     
     
         23 : The method of  claim 14 , further comprising administering an agent to the subject prior to administering the molecular probe to the subject and comparing the detected amount or distribution of the molecular probe in the tissue of interest to a control amount or distribution, wherein a decrease in the detected amount or distribution of the molecular probe in the tissue of interest is indicative of the agent reducing the sphingolipids in the tissue of interest. 
     
     
         24 : The method of  claim 23 , the agent administered to the subject being screened for efficacy in treating aberrant lipid accumulation associated with a lipid storage disease. 
     
     
         25 : The method of  claim 24 , wherein the lipid storage disease is Fabry disease. 
     
     
         26 - 33 . (canceled)